in degenerative joint diseases, the articiilating surfaces of a joint are gradually destroyed, ultimately resulting in pain and joint dysfunction. Most degenerative joint diseases are chronic pathologies: that are [unreadable] driven by disease processes occurring over years, and while end-stage disease can be described by cartilage loss, subchondral bone remodeling, dysfunction, and pain, the initiating stages do not always have a clear etiology. As a result, disease modifying strategies are faced with a diverse blend of chronic disease processes that have potentially risen from a number of cbhnplex origins. The goal of the ROO phase of this K99/R00 application is to Investigate local regulation of catabolic and pro-inflammatory mediators in the rat temporomandibular joint (TMJ) and the subsequent development of pain related behaviors and TMJ dysfunction. This work represents the transition of a K99/R00 award to the independent ROO phase. During K99 training, the PI investigated the local regulation of disease factors associated with knee arthritis and developed new quantitative gait measures of knee dysfunction for the rat pre-clinical model. In the ROO phase, a similar approach is proposed for the study of degenerative! pathology in the TMJ. First, we will develop new methods to assessib^haviors associated with TMJ pain and dysfunction in the rat, including new systems to assess chewing kjhematics, dietary habits,^ bite-force, sleeping and grooming behaviorSi and orofacial sensitivity. Concurrently, we will develop a model of chronic TMJ degeneration using ihtra-articular injection of sodium monoioddacetate (MIA);here, TMJ degeneration induced by MIA will occur over a period of weeks, simulating .the Chronic cascade of TMJ arthritis, in this model, we will investigate catabolic and pro-imflammatory rriarkers of TMJ pathology in thes serum, saliva, and TMJ synovial fluid. F'ihally, we will combine behavioral analysis tools with our model;of TMJ degeneration to examine tliei relatidnship between local regulation of disease processes and the development of disease sequelae associated with TMJ degeheration. With this work, we aim to identify critical features, stages,/and; mediators of TMJ degeheration with the goal of developing future interventional studies.